Mechanisms of cyclooxygenase2 expression-induced by oxidized-LDL in VSMC

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In 2001, proliferation of vascular smooth muscle cells (VSMC) were found to be mediated through cyclooxygenase 2 (COX2) expression-induced by Oxidized LDL. We also identified that COX2 expression was dependent on the activation of p42/44MAPK and p38MAPK. In 2002, in order to elucidate the regulation of transcription of COX2 and novel pathways besides MAPKs, we performed following experiments. First, we examined the role of p42/44MAPK and p38MAPK on cox2 mRNA expression. We identified that p42/44MAPK was related with transcription of cox2 and p38MAPK was associated with the stabilization of cox2 mRNA. Second, Dr Eguchi found that mRNA expression of helix-loop helix Id3 aw well as p21WAP/Cip1 and p27Kip1 were enhanced by oxidized-LDL stimulation in VSMC. It is very interesting that all of them were cell cycle related genes. Therefore, we need to do further investigation of the signaling pathway of these genes-induced by oxidized-LDL to identify the mechanisms of growth of VSMC.